Clinical Trials for Sale

The net is alive with the case of The Burzynski Research Institute. It’s actually a very old story, but has had new life breathed into it by an article in The Observer. There is of course a very great deal that this article does not say. At least the author makes it clear that the treatment antineoplaston (ANP) is experimental, and that there is only a small chance of success. How small however is not said, but what is very large is how much a patient has to pay to get into a clinical trial conducted by The Burzynski Research Institute (BRI). In 35 years of clinical science, I have never heard of anyone having to pay to enter a clinical trial, let alone the £200,000 quoted here. This seems well worth looking into.

Well more eminent bloggers than I have done just that. The inestimable Andy Lewis, of Quackometer fame, was among the first to wade in, and has been rewarded with probably the most scurrilous and puerile attack I have ever seen from the pseudoscience fraternity. The non-lawyer Marc Stephens accuses Andy of lying and fraud. OK, let’s see who is telling the truth.

There are 61 protocols on http://www.clinicaltrials.gov, going back to 1999 when the website started. Of these, one is given as completed, six as withdrawn, 10 actively recruiting patients, and 34 of unknown status. The remainder are shown as not recruiting. A search of PubMed reveals five citations for clinical trials, under the authorship of S Burzynski:

  1. Burzynski SR, Kubove E, Burzynski B. Treatment of hormonally refractory cancer of the prostate with antineoplaston AS2-1. Drugs Exp Clin Res. 1990;16(7):361-9.
  2. Burzynski SR, Lewy RI, Weaver RA, Axler ML, Janicki TJ, Jurida GF, Paszkowiak JK, Szymkowski BG, Khan MI, Bestak M. Phase II study of antineoplaston A10 and AS2-1 in patients with recurrent diffuse intrinsic brain stem glioma: a preliminary report. Drugs R D. 2003;4(2):91-101.
  3. Burzynski SR, Weaver RA, Lewy RI, Janicki TJ, Jurida GF, Szymkowski BG, Khan MI, Bestak M. Phase II study of antineoplaston A10 and AS2-1 in children with recurrent and progressive multicentric glioma : a preliminary report. Drugs R D. 2004;5(6):315-26.
  4. Burzynski SR, Weaver RA, Janicki T, Szymkowski B, Jurida G, Khan M, Dolgopolov V. Long-term survival of high-risk pediatric patients with primitive neuroectodermal tumors treated with antineoplastons A10 and AS2-1. Integr Cancer Ther. 2005 Jun;4(2):168-77.
  5. Burzynski SR, Janicki TJ, Weaver RA, Burzynski B. Targeted therapy with antineoplastons A10 and AS2-1 of high-grade, recurrent, and progressive brainstem glioma. Integr Cancer Ther. 2006 Mar;5(1):40-7.

None is a controlled clinical trial. They are all case series with no more than 14 patients each. Three of them seem to include the same patients – they are periodic reports on the same study. In publication 5, the authors conclude:

Antineoplastons contributed to more than a 5-year survival in recurrent diffuse intrinsic glioblastomas and anaplastic astrocytomas of the brainstem in a small group of patients.

This is a staggeringly confident assumption of causality, in the absence of any control group.

The abstract for publication 2 states:

The percentage of patients’ response is lower than for standard treatment of favorable PNET, but long-term survival in poor-risk cases and reduced toxicity makes ANP promising for very young children, patients at high risk of complication of standard therapy, and patients with recurrent tumors.

Again, it is impossible for anyone to draw any conclusions as to survival, in the absence of a control group. The abstract does not define `response’, but even so the authors admit that whatever the criterion, the treatment was less effective that standard therapy. Is this all there is to show for 21 years of `research’? Out of 61 protocols we have only seen five publications. Note that there has been nothing for the last five years. So far, we have no evidence (at least as available on PubMed) of any clear benefit. Indeed, one attempt to conduct a properly designed trial ended in disarray because the sponsor (The National Cancer Institute) and Dr Burzynski disagreed on scientific protocols.

But while researching BRI’s claim to have FDA approval for a phase III trial*, I came across more interesting stuff. On 5th October 2009 The FDA issued a warning letter, after a regulatory inspection of the BRI institutional review board (IRB). I should explain that in the USA an IRB is effectively what we call an ethics committee. In this case, BRI has its own IRB, which is supposed to be independent. The primary purpose of the IRB is to protect clinical trial patients from ethical abuses. To summarise the letter, the main violations were:

  • Failing to report to the FDA that BRI had dosed human subjects without IRB approval.
  • Allowing a study to proceed, despite asking for further pre-clinical toxicology data.
  • Allowing a study to proceed without an investigator’s brochure having been submitted (the investigator’s brochure is the detailed summary of all data to date, and is mandatory for all investigational drugs).
  • Approving the use of a medical device without assessment of risk.
  • Failing to ensure that BRI obtained informed consent from patients or guardians.
  • Conflict of interest between BRI and the IRB – the IRB chairman was also an investigator.
  • Failing to carry out regular review of ongoing studies.
  • Multiple failures to maintain files and documents, including minutes of meetings.
  • Co-opting external people onto the IRB, against FDA rules.

Note that the FDA has not issued a close-out letter, hence the IRB has so far failed to remedy these breaches. Yet BRI continues to dose patients with its unproven treatment nearly three years after the inspection. What does the FDA think it is doing? Surely it’s time for a `for-cause’ inspection of BRI itself?

Isn’t it significant that among enthusiasts for pseudoscientific medicine there are so many deeply unpleasant people? For example, I have on occasion crossed swords with the homeopath John Benneth, and have received a threatening phone call from a certain academic who will remain nameless – unless he tries it again. How many real scientists behave like this? OK, I know that Isaac Newton was very nasty to Leibniz, but Newton was exceptional in many ways. Marc Stephens and his ilk always remind me of what little Shakespeare I remember – “Methinks [he] doth protest too much”.

*How is it possible to go to phase III trials without any proof of concept or dose-ranging data?

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9 Responses

  1. [...] Clinical Trials for Sale Majikthyse, 28/11/11 [...]

  2. [...] analysis of Burzynski’s trials is here – clinical trials for sale (“Clinical Trials for Sale [...]

  3. [...] Majikthyse – Clinical Trials for Sale [...]

  4. [...] Clinical Trials for Sale Majikthyse, 28/11/11 [...]

  5. I suspect the FDA is allowing a Phase 3 trial to force Burzynski to do a decent controlled trial in collaboration with a real cancer unit (as Burzynski can’t do scans or give radiation therapy). Hence why the trial hasn’t started and probably never will. Slightly twisted rationale if you ask me, they should have demanded results a long time ago. The fact they’ve been so lax puts the lie to Burzynski’s claims of being buried by the FDA though.

    • Over 2 months now since my FOI request to FDA for phase II results that allowed phase III trials to be authorised. What is the time limit for the US FOI Act?

    • Perpetuating a myth doesn’t make it any more valid. Were such an article to appear in a peer-reviewed journal, I might take some notice, but your “unpalatable truth” is simply asserted without a shred of evidence. What on earth are you saying? What is all this about antineoplastons being about to emerge? They have been `emerging’ for 30 years, without any credible evidence that they do anything. Meanwhile, Burzynski rips off desperate patients by charging them grossly inflated prices for the standard chemotherapy drugs that you denigrate. If you can’t see a scam a mile off then your eyes are closed.

  6. [...] Majikthyse – Clinical Trials for Sale [...]

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